In this research project we will study the chemical mechanism of estrogen induction of renal clear cell carcinomas in Syrian hamster. It has been shown that among the steroid hormones tested, estrogens alone are capable of inducing these kidney tubule tumors, and that the induction is tissue specific in that only kidney tumors develop and not tumors in other tissues. Natural and synthetic estrogens are equally potent in tumor induction. Our purpose is to establish the molecular basis for the tumor induction by; (1) studying the metabolism of diethylstilbestrol in hamster, identifying and characterizing these metabolites, (2) determining whether allylic alcohol metabolites or semiquinone-quinone metabolites are the active adduct forming compounds with the bases of DNA, (3) determining whether the inactive (congugated) metabolites are delivered to kidney, followed by subsequent activation by deconjugation, (4) determining the nucleoside specificity of adduct formation (i.e., guanosine, adenosine, thymidine, or cytidine) (5) establishing if adduct formation by any diethylstilbestrol metabolite correlates with carcinogenicity, and (6) establishing the chemical structures of adducts by separation with high pressure liquid chromatography, followed by mass spectrometry procedures and NMR analysis. Finally, attempts will be made to block diethylstilbestrol carcinogenesis with reducing substances which may react with the active metabolites blocking their carcinogenic activity. The overall goal of this project is to establish that diethylstilbestrol can function as a DNA altering material similar to other chemical carcinogens, and to begin to explore the chemical nature and frequency of specific DNA base adducts.